COMPOUND HETEROZYGOTE REASON FOR JUVENILE FORM OF TAY-SACHIS DISEASE -CASE REPORT
Abstract
Tay-Sachs diseases are group of rare autosomal recessive lysosomal disorders, GM2-gangliozidoses. They are progressive neurodegenerative diseases, caused by a mutation in the enzyme β-hexosaminidase A. Depending on the time of presentation of symptoms, there are three forms: infantile, juvenile and adult. We present a 8 year old patient, who is presented at the age of 4 with progressive deterioration in psychomotor and speech skills, pyramidal symptoms, ataxia and muscle weakness. The EEG showed bihemispheric fast spike waves and the MRI showed no findings of organic disease. Finally a molecular genetic testing was made, which proved the diagnosis of juvenile form of Tay-Sachs disease. It was determined that the patient is a compound heterozygote, with two different mutations in the alleles of the HEXA gene, one inherited from the mother and the other one from the father. The juvenile Tay-Sachs disease is characterized with beginnig between the age of 2 to 10 years old. Clinically it is presented with muscle weakness, incoordination, ataxia, dysarthria, dysphagia and progressive spasticity. It progresses to development of dementia, convulsions, blindness and vegetative state with decerebrate rigidity and death by the age of 15. It is inherited autosomal recessive with one mutation present on both alleles of the HEXA gene. Treatment options for Tay-Sachs disease currently are only symptomatic and supportive. There are ongoing researches for curative treatments for Tay-Sachs, like enzyme replacement, chaperone, substrate reduction and gene therapy.
Keywords: Tay-Sachs disease, juvenile form, compound heterozygote.
References
2. Lawson CA, Martin DR. Animal models of GM2 gangliosidosis: utility and limitations. ApplClin Genet. 2016 Jul 20;9:111-20.
3. Park JH, Ko JM, Kim MS, Kim MJ, Seong MW, Yoo T, Lim BC, Chae JH. Novel HEXA variants in Korean children with Tay-Sachs disease with regression of neurodevelopment from infancy. Mol Genet Genomic Med. 2021 Jun;9(6):e1677.
4. Hechtman P, Kaplan F. Tay-Sachs disease screening and diagnosis: evolving technologies. DNA Cell Biol. 1993 Oct12(8):651-65.
5. Sheth J, Mistri M, Mahadevan L et al. Identification of deletion-duplication in HEXA gene in five children with Tay-Sachs disease from India. BMC Med Genet.2018 Jul 4;19(1):109
6. Lew RM, Burnett L, Proos AL, Delatycki MB. Tay-Sachs disease: current perspectives from Australia. ApplClin Genet. 2015 Jan 21;8:19-25.
7. Myerowitz R. Tay-Sachs disease-causing mutations and neutral polymorphisms in the Hex A gene. Hum Mutat. 1997;9(3):195-208.
8. Boles DJ, Proia RL. The molecular basis of HEXA mRNA deficiency caused by the most common Tay-Sachs disease mutation. Am J Hum Genet. 1995;56(3):716-724.
9. Park N, Morgan C, Sharma R et al. Improving Accuracy of Tay Sachs Carrier Screening of the Non-Jewish Population: Analysis of 34 Carriers and Six Late-Onset Patients With HEXA Enzyme and DNA Sequence Analysis. Pediatr Res.2010 Feb; 67:217–220.
10. Solovyeva VV, Shaimardanova AA, Chulpanova DS, Kitaeva KV, Chakrabarti L, Rizvanov AA. New Approaches to Tay-Sachs Disease Therapy. Front Physiol. 2018 Nov 20;9:1663.
11. Leal AF, Benincore-Flórez E, Solano-Galarza D, Garzón Jaramillo RG, Echeverri-Peña OY, Suarez DA, Alméciga-DÃaz CJ, Espejo-Mojica AJ. GM2 Gangliosidoses: Clinical Features, Pathophysiological Aspects, and Current Therapies. Int J Mol Sci. 2020 Aug 27;21(17):6213.
12. Flotte TR, Cataltepe O, Puri A, Batista AR, Moser R, McKenna-Yasek Det al. AAV gene therapy for Tay-Sachs disease. Nat Med. 2022 Feb;28(2):251-259.
